NPASS Compound

Structure

NPC272451 OpenBabel07101719142D 35 38 0 0 1 0 0 0 0 0999 V2000 -4.3950 1.6347 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1270 -1.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6270 -2.2314 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2256 0.5902 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0766 1.5791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7997 0.2094 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8591 -0.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6629 -1.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3950 -0.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5289 0.1347 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2658 1.8565 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9309 -1.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9459 1.1235 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7969 -1.8653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9931 -1.8653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8591 -1.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9931 1.1347 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2610 1.1347 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2610 0.1347 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9931 0.1347 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.1270 1.6347 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6629 -0.3653 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2686 1.7818 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9309 -0.3653 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.1270 -0.3653 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.1270 -1.3653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2948 0.9556 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7969 0.1347 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.8591 -0.3653 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6629 -1.3653 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.1270 2.6347 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2314 2.6478 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3591 0.5007 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1629 -2.2314 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 26 1 0 0 0 0 3 26 1 0 0 0 0 4 27 1 0 0 0 0 5 27 1 0 0 0 0 9 10 1 0 0 0 0 9 19 2 0 0 0 0 10 22 1 0 0 0 0 11 13 1 0 0 0 0 11 23 1 0 0 0 0 12 14 1 0 0 0 0 12 24 1 0 0 0 0 13 28 1 0 0 0 0 14 30 1 0 0 0 0 15 16 1 0 0 0 0 15 26 1 0 0 0 0 16 29 1 0 0 0 0 17 20 1 0 0 0 0 17 21 1 0 0 0 0 18 1 1 1 0 0 0 18 19 1 0 0 0 0 18 21 1 0 0 0 0 20 25 1 0 0 0 0 20 29 1 1 0 0 0 21 31 2 0 0 0 0 22 28 1 1 0 0 0 22 30 1 0 0 0 0 23 27 1 0 0 0 0 23 32 1 6 0 0 0 24 28 1 1 0 0 0 24 35 1 0 0 0 0 25 19 1 1 0 0 0 25 26 1 0 0 0 0 27 35 1 0 0 0 0 28 6 1 1 0 0 0 29 7 1 1 0 0 0 29 33 1 0 0 0 0 30 8 1 1 0 0 0 30 34 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	490.37
Volume:	531.888
LogP:	5.57
LogD:	3.968
LogS:	-3.19
# Rotatable Bonds:	3
TPSA:	86.99
# H-Bond Aceptor:	5
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.497
Synthetic Accessibility Score:	5.245
Fsp3:	0.9
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.706
MDCK Permeability:	1.4153586562315468e-05
Pgp-inhibitor:	0.999
Pgp-substrate:	0.024
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.941
30% Bioavailability (F30%):	0.892

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.373
Plasma Protein Binding (PPB):	84.43009185791016%
Volume Distribution (VD):	0.791
Pgp-substrate:	10.398505210876465%

ADMET: Metabolism

CYP1A2-inhibitor:	0.005
CYP1A2-substrate:	0.132
CYP2C19-inhibitor:	0.025
CYP2C19-substrate:	0.831
CYP2C9-inhibitor:	0.067
CYP2C9-substrate:	0.031
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.07
CYP3A4-inhibitor:	0.624
CYP3A4-substrate:	0.542

ADMET: Excretion

Clearance (CL):	15.289
Half-life (T1/2):	0.049

ADMET: Toxicity

hERG Blockers:	0.062
Human Hepatotoxicity (H-HT):	0.327
Drug-inuced Liver Injury (DILI):	0.035
AMES Toxicity:	0.013
Rat Oral Acute Toxicity:	0.815
Maximum Recommended Daily Dose:	0.938
Skin Sensitization:	0.572
Carcinogencity:	0.919
Eye Corrosion:	0.007
Eye Irritation:	0.012
Respiratory Toxicity:	0.984

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC272451

Natural Product ID:	NPC272451
*Common Name:**	Sipholenol J
IUPAC Name:	(3S,4Z,4aR,8S,8aS)-4-[2-[(3S,5aS,6S,7S,9aS)-3,7-dihydroxy-2,2,5a,7-tetramethyl-4,5,6,8,9,9a-hexahydro-3H-benzo[b]oxepin-6-yl]ethylidene]-8-hydroxy-3,5,5,8-tetramethyl-4a,6,7,8a-tetrahydro-1H-naphthalen-2-one
Synonyms:	Sipholenol J
Standard InCHIKey:	MHHGQQXZBFDTSD-WSBLRCOQSA-N
Standard InCHI:	InChI=1S/C30H50O5/c1-18-19(25-20(17-21(18)31)29(7,33)16-15-26(25,2)3)9-10-22-28(6)13-11-23(32)27(4,5)35-24(28)12-14-30(22,8)34/h9,18,20,22-25,32-34H,10-17H2,1-8H3/b19-9+/t18-,20-,22-,23-,24-,25+,28-,29-,30-/m0/s1
SMILES:	C[C@@H]1C(=O)C[C@H]2[C@@H](/C/1=C/C[C@@H]1[C@@](C)(O)CC[C@H]3[C@@]1(C)CC[C@@H](C(O3)(C)C)O)C(C)(C)CC[C@]2(C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL563310
PubChem CID:	44234696
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001729] Oxepanes

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17488128]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19534474]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Others	2

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT668	Individual Protein	P-glycoprotein 1	Homo sapiens	Ratio IC50	=	0.8	n.a.	PMID[556200]
NPT668	Individual Protein	P-glycoprotein 1	Homo sapiens	Ratio IC50	=	300.0	n.a.	PMID[556200]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC272451 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	231
0.1-0.2	1472
0.2-0.3	4806
0.3-0.4	9671
0.4-0.5	12445
0.5-0.6	6181
0.6-0.7	5719
0.7-0.8	2143
0.8-0.85	25
0.85-0.9	2
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9247	High Similarity	NPC91439
0.8791	High Similarity	NPC189777
0.8632	High Similarity	NPC293086
0.837	Intermediate Similarity	NPC290731
0.8333	Intermediate Similarity	NPC477877
0.83	Intermediate Similarity	NPC54909
0.83	Intermediate Similarity	NPC233012
0.8298	Intermediate Similarity	NPC193360
0.8247	Intermediate Similarity	NPC103527
0.8229	Intermediate Similarity	NPC473166
0.8229	Intermediate Similarity	NPC210268
0.82	Intermediate Similarity	NPC167974
0.8191	Intermediate Similarity	NPC233744
0.8182	Intermediate Similarity	NPC43686
0.8182	Intermediate Similarity	NPC259788
0.8182	Intermediate Similarity	NPC255589
0.8163	Intermediate Similarity	NPC474727
0.8163	Intermediate Similarity	NPC279974
0.8155	Intermediate Similarity	NPC102352
0.8155	Intermediate Similarity	NPC472655
0.8144	Intermediate Similarity	NPC274046
0.8144	Intermediate Similarity	NPC198074
0.8137	Intermediate Similarity	NPC478057
0.8137	Intermediate Similarity	NPC471005
0.8137	Intermediate Similarity	NPC194323
0.8131	Intermediate Similarity	NPC477266
0.8125	Intermediate Similarity	NPC232202
0.8119	Intermediate Similarity	NPC476897
0.8119	Intermediate Similarity	NPC256247
0.8105	Intermediate Similarity	NPC472802
0.81	Intermediate Similarity	NPC119036
0.81	Intermediate Similarity	NPC470066
0.81	Intermediate Similarity	NPC470067
0.8095	Intermediate Similarity	NPC310546
0.8095	Intermediate Similarity	NPC87335
0.8085	Intermediate Similarity	NPC476217
0.8085	Intermediate Similarity	NPC74363
0.8085	Intermediate Similarity	NPC475862
0.8085	Intermediate Similarity	NPC73038
0.8081	Intermediate Similarity	NPC19376
0.8081	Intermediate Similarity	NPC307282
0.8081	Intermediate Similarity	NPC230151
0.8081	Intermediate Similarity	NPC305464
0.8081	Intermediate Similarity	NPC327179
0.8081	Intermediate Similarity	NPC256227
0.8081	Intermediate Similarity	NPC158371
0.8081	Intermediate Similarity	NPC207922
0.8081	Intermediate Similarity	NPC259733
0.8081	Intermediate Similarity	NPC25848
0.8081	Intermediate Similarity	NPC260223
0.8077	Intermediate Similarity	NPC144854
0.8077	Intermediate Similarity	NPC473173
0.8077	Intermediate Similarity	NPC230541
0.8077	Intermediate Similarity	NPC3316
0.8077	Intermediate Similarity	NPC469318
0.8061	Intermediate Similarity	NPC174051
0.8061	Intermediate Similarity	NPC67831
0.8058	Intermediate Similarity	NPC475036
0.8058	Intermediate Similarity	NPC470838
0.8058	Intermediate Similarity	NPC471293
0.8043	Intermediate Similarity	NPC212083
0.8041	Intermediate Similarity	NPC105189
0.8041	Intermediate Similarity	NPC198054
0.8041	Intermediate Similarity	NPC473167
0.8037	Intermediate Similarity	NPC474516
0.8037	Intermediate Similarity	NPC46388
0.8037	Intermediate Similarity	NPC234042
0.8037	Intermediate Similarity	NPC37739
0.8037	Intermediate Similarity	NPC152117
0.8021	Intermediate Similarity	NPC115607
0.8021	Intermediate Similarity	NPC97103
0.8021	Intermediate Similarity	NPC229871
0.8021	Intermediate Similarity	NPC32830
0.8021	Intermediate Similarity	NPC469319
0.802	Intermediate Similarity	NPC477655
0.802	Intermediate Similarity	NPC477656
0.8019	Intermediate Similarity	NPC250956
0.8019	Intermediate Similarity	NPC470065
0.8	Intermediate Similarity	NPC73064
0.8	Intermediate Similarity	NPC476879
0.8	Intermediate Similarity	NPC258323
0.8	Intermediate Similarity	NPC277017
0.8	Intermediate Similarity	NPC469314
0.8	Intermediate Similarity	NPC154608
0.8	Intermediate Similarity	NPC469317
0.8	Intermediate Similarity	NPC477926
0.8	Intermediate Similarity	NPC9613
0.8	Intermediate Similarity	NPC247139
0.8	Intermediate Similarity	NPC192813
0.8	Intermediate Similarity	NPC476878
0.8	Intermediate Similarity	NPC241875
0.7981	Intermediate Similarity	NPC470587
0.798	Intermediate Similarity	NPC473415
0.798	Intermediate Similarity	NPC30677
0.798	Intermediate Similarity	NPC180557
0.798	Intermediate Similarity	NPC469329
0.798	Intermediate Similarity	NPC37787
0.798	Intermediate Similarity	NPC96916
0.798	Intermediate Similarity	NPC53565
0.7979	Intermediate Similarity	NPC133954
0.7963	Intermediate Similarity	NPC204458
0.7963	Intermediate Similarity	NPC271138
0.7963	Intermediate Similarity	NPC47063
0.7963	Intermediate Similarity	NPC317210
0.7963	Intermediate Similarity	NPC138334
0.7963	Intermediate Similarity	NPC189884
0.7963	Intermediate Similarity	NPC269315
0.7961	Intermediate Similarity	NPC282233
0.7961	Intermediate Similarity	NPC277074
0.7961	Intermediate Similarity	NPC95585
0.7961	Intermediate Similarity	NPC90177
0.7961	Intermediate Similarity	NPC209298
0.7959	Intermediate Similarity	NPC307335
0.7959	Intermediate Similarity	NPC74855
0.7959	Intermediate Similarity	NPC158059
0.7959	Intermediate Similarity	NPC275809
0.7959	Intermediate Similarity	NPC136313
0.7959	Intermediate Similarity	NPC202728
0.7959	Intermediate Similarity	NPC199543
0.7959	Intermediate Similarity	NPC118490
0.7959	Intermediate Similarity	NPC118519
0.7944	Intermediate Similarity	NPC191763
0.7941	Intermediate Similarity	NPC118964
0.7941	Intermediate Similarity	NPC476132
0.7941	Intermediate Similarity	NPC477051
0.7941	Intermediate Similarity	NPC477053
0.7941	Intermediate Similarity	NPC252614
0.7941	Intermediate Similarity	NPC477052
0.7941	Intermediate Similarity	NPC97435
0.7938	Intermediate Similarity	NPC291028
0.7938	Intermediate Similarity	NPC210037
0.7938	Intermediate Similarity	NPC18872
0.7938	Intermediate Similarity	NPC120968
0.7938	Intermediate Similarity	NPC273621
0.7938	Intermediate Similarity	NPC227467
0.7938	Intermediate Similarity	NPC290614
0.7938	Intermediate Similarity	NPC193750
0.7938	Intermediate Similarity	NPC477872
0.7938	Intermediate Similarity	NPC7260
0.7925	Intermediate Similarity	NPC237503
0.7925	Intermediate Similarity	NPC204407
0.7925	Intermediate Similarity	NPC218853
0.7925	Intermediate Similarity	NPC57362
0.7925	Intermediate Similarity	NPC137917
0.7925	Intermediate Similarity	NPC306746
0.7925	Intermediate Similarity	NPC167383
0.7925	Intermediate Similarity	NPC141350
0.7921	Intermediate Similarity	NPC191565
0.7921	Intermediate Similarity	NPC477875
0.7921	Intermediate Similarity	NPC477876
0.7921	Intermediate Similarity	NPC58942
0.7921	Intermediate Similarity	NPC260149
0.7917	Intermediate Similarity	NPC470417
0.7905	Intermediate Similarity	NPC67321
0.7905	Intermediate Similarity	NPC187435
0.7905	Intermediate Similarity	NPC283849
0.7905	Intermediate Similarity	NPC293512
0.7905	Intermediate Similarity	NPC59530
0.79	Intermediate Similarity	NPC173744
0.79	Intermediate Similarity	NPC29410
0.79	Intermediate Similarity	NPC200054
0.79	Intermediate Similarity	NPC469545
0.79	Intermediate Similarity	NPC157113
0.79	Intermediate Similarity	NPC204961
0.79	Intermediate Similarity	NPC61369
0.79	Intermediate Similarity	NPC62516
0.79	Intermediate Similarity	NPC5532
0.79	Intermediate Similarity	NPC73004
0.79	Intermediate Similarity	NPC473158
0.7895	Intermediate Similarity	NPC325594
0.7895	Intermediate Similarity	NPC324063
0.7895	Intermediate Similarity	NPC213412
0.789	Intermediate Similarity	NPC477580
0.789	Intermediate Similarity	NPC247069
0.789	Intermediate Similarity	NPC326542
0.7885	Intermediate Similarity	NPC222161
0.7885	Intermediate Similarity	NPC29705
0.7885	Intermediate Similarity	NPC65523
0.7885	Intermediate Similarity	NPC301787
0.7885	Intermediate Similarity	NPC121566
0.7885	Intermediate Similarity	NPC100955
0.7879	Intermediate Similarity	NPC196227
0.7879	Intermediate Similarity	NPC32407
0.7879	Intermediate Similarity	NPC114159
0.7879	Intermediate Similarity	NPC88116
0.7879	Intermediate Similarity	NPC20235
0.7879	Intermediate Similarity	NPC111015
0.7879	Intermediate Similarity	NPC6818
0.7879	Intermediate Similarity	NPC296164
0.7879	Intermediate Similarity	NPC263548
0.7879	Intermediate Similarity	NPC299996
0.7879	Intermediate Similarity	NPC231063
0.7879	Intermediate Similarity	NPC145667
0.7879	Intermediate Similarity	NPC209662
0.7879	Intermediate Similarity	NPC191412
0.7879	Intermediate Similarity	NPC282395
0.787	Intermediate Similarity	NPC256798
0.787	Intermediate Similarity	NPC472002
0.787	Intermediate Similarity	NPC116794
0.787	Intermediate Similarity	NPC128925

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC272451 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	204
0.1-0.2	1788
0.2-0.3	3858
0.3-0.4	2182
0.4-0.5	673
0.5-0.6	201
0.6-0.7	221
0.7-0.8	23
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7822	Intermediate Similarity	NPD7902	Approved
0.7708	Intermediate Similarity	NPD3618	Phase 1
0.77	Intermediate Similarity	NPD7748	Approved
0.7677	Intermediate Similarity	NPD7515	Phase 2
0.7664	Intermediate Similarity	NPD5345	Clinical (unspecified phase)
0.76	Intermediate Similarity	NPD6399	Phase 3
0.7593	Intermediate Similarity	NPD8132	Clinical (unspecified phase)
0.7573	Intermediate Similarity	NPD7638	Approved
0.757	Intermediate Similarity	NPD6412	Phase 2
0.7525	Intermediate Similarity	NPD7901	Clinical (unspecified phase)
0.7525	Intermediate Similarity	NPD7900	Approved
0.75	Intermediate Similarity	NPD4786	Approved
0.75	Intermediate Similarity	NPD7640	Approved
0.75	Intermediate Similarity	NPD7639	Approved
0.7477	Intermediate Similarity	NPD4632	Approved
0.7475	Intermediate Similarity	NPD5328	Approved
0.7474	Intermediate Similarity	NPD3667	Approved
0.7447	Intermediate Similarity	NPD7525	Registered
0.7431	Intermediate Similarity	NPD4061	Clinical (unspecified phase)
0.7426	Intermediate Similarity	NPD4202	Approved
0.735	Intermediate Similarity	NPD8328	Phase 3
0.7327	Intermediate Similarity	NPD8035	Phase 2
0.7327	Intermediate Similarity	NPD6079	Approved
0.7327	Intermediate Similarity	NPD8034	Phase 2
0.7315	Intermediate Similarity	NPD6402	Approved
0.7315	Intermediate Similarity	NPD7128	Approved
0.7315	Intermediate Similarity	NPD5739	Approved
0.7315	Intermediate Similarity	NPD6675	Approved
0.7308	Intermediate Similarity	NPD4755	Approved
0.7273	Intermediate Similarity	NPD6373	Approved
0.7273	Intermediate Similarity	NPD6372	Approved
0.7241	Intermediate Similarity	NPD6319	Approved
0.7241	Intermediate Similarity	NPD6054	Approved
0.7241	Intermediate Similarity	NPD6059	Approved
0.7232	Intermediate Similarity	NPD8297	Approved
0.7212	Intermediate Similarity	NPD4697	Phase 3
0.7207	Intermediate Similarity	NPD5955	Clinical (unspecified phase)
0.7207	Intermediate Similarity	NPD4634	Approved
0.7182	Intermediate Similarity	NPD7320	Approved
0.7182	Intermediate Similarity	NPD6881	Approved
0.7182	Intermediate Similarity	NPD6899	Approved
0.7182	Intermediate Similarity	NPD6686	Approved
0.717	Intermediate Similarity	NPD5286	Approved
0.717	Intermediate Similarity	NPD4696	Approved
0.717	Intermediate Similarity	NPD4700	Approved
0.717	Intermediate Similarity	NPD5285	Approved
0.7158	Intermediate Similarity	NPD7645	Phase 2
0.7156	Intermediate Similarity	NPD6008	Approved
0.7143	Intermediate Similarity	NPD3665	Phase 1
0.7143	Intermediate Similarity	NPD3133	Approved
0.7143	Intermediate Similarity	NPD6649	Approved
0.7143	Intermediate Similarity	NPD6650	Approved
0.7143	Intermediate Similarity	NPD3666	Approved
0.713	Intermediate Similarity	NPD6009	Approved
0.713	Intermediate Similarity	NPD7115	Discovery
0.713	Intermediate Similarity	NPD8295	Clinical (unspecified phase)
0.7119	Intermediate Similarity	NPD6370	Approved
0.7103	Intermediate Similarity	NPD5223	Approved
0.7091	Intermediate Similarity	NPD5697	Approved
0.7091	Intermediate Similarity	NPD5701	Approved
0.7083	Intermediate Similarity	NPD7507	Approved
0.7071	Intermediate Similarity	NPD7520	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD7604	Phase 2
0.7054	Intermediate Similarity	NPD7290	Approved
0.7054	Intermediate Similarity	NPD7102	Approved
0.7054	Intermediate Similarity	NPD6883	Approved
0.7048	Intermediate Similarity	NPD5220	Clinical (unspecified phase)
0.7048	Intermediate Similarity	NPD5222	Approved
0.7048	Intermediate Similarity	NPD5221	Approved
0.7037	Intermediate Similarity	NPD5224	Approved
0.7037	Intermediate Similarity	NPD5211	Phase 2
0.7037	Intermediate Similarity	NPD5225	Approved
0.7037	Intermediate Similarity	NPD5226	Approved
0.7037	Intermediate Similarity	NPD4633	Approved
0.7034	Intermediate Similarity	NPD6016	Approved
0.7034	Intermediate Similarity	NPD5983	Phase 2
0.7034	Intermediate Similarity	NPD6015	Approved
0.7027	Intermediate Similarity	NPD6011	Approved
0.7018	Intermediate Similarity	NPD8133	Approved
0.7	Intermediate Similarity	NPD3574	Clinical (unspecified phase)
0.7	Intermediate Similarity	NPD7492	Approved
0.6991	Remote Similarity	NPD6847	Approved
0.6991	Remote Similarity	NPD6617	Approved
0.6991	Remote Similarity	NPD6869	Approved
0.6991	Remote Similarity	NPD8130	Phase 1
0.6991	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.6981	Remote Similarity	NPD6084	Phase 2
0.6981	Remote Similarity	NPD5173	Approved
0.6981	Remote Similarity	NPD6083	Phase 2
0.6975	Remote Similarity	NPD5988	Approved
0.6972	Remote Similarity	NPD4754	Approved
0.6972	Remote Similarity	NPD5174	Approved
0.6972	Remote Similarity	NPD5175	Approved
0.697	Remote Similarity	NPD3668	Phase 3
0.6967	Remote Similarity	NPD7736	Approved
0.6964	Remote Similarity	NPD6014	Approved
0.6964	Remote Similarity	NPD6012	Approved
0.6964	Remote Similarity	NPD6013	Approved
0.6961	Remote Similarity	NPD4753	Phase 2
0.6942	Remote Similarity	NPD6336	Discontinued
0.6942	Remote Similarity	NPD6616	Approved
0.6937	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.693	Remote Similarity	NPD6882	Approved
0.6923	Remote Similarity	NPD7327	Approved
0.6923	Remote Similarity	NPD7328	Approved
0.6917	Remote Similarity	NPD6067	Discontinued
0.6916	Remote Similarity	NPD4225	Approved
0.6911	Remote Similarity	NPD7319	Approved
0.6909	Remote Similarity	NPD5141	Approved
0.6891	Remote Similarity	NPD6921	Approved
0.6885	Remote Similarity	NPD7078	Approved
0.6885	Remote Similarity	NPD8293	Discontinued
0.6881	Remote Similarity	NPD7632	Discontinued
0.6869	Remote Similarity	NPD4788	Approved
0.6864	Remote Similarity	NPD7516	Approved
0.6863	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6847	Remote Similarity	NPD4768	Approved
0.6847	Remote Similarity	NPD4767	Approved
0.6832	Remote Similarity	NPD6684	Approved
0.6832	Remote Similarity	NPD7334	Approved
0.6832	Remote Similarity	NPD6409	Approved
0.6832	Remote Similarity	NPD7521	Approved
0.6832	Remote Similarity	NPD7146	Approved
0.6832	Remote Similarity	NPD5330	Approved
0.6829	Remote Similarity	NPD6033	Approved
0.6792	Remote Similarity	NPD5210	Approved
0.6792	Remote Similarity	NPD4629	Approved
0.6792	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6768	Remote Similarity	NPD4223	Phase 3
0.6768	Remote Similarity	NPD4221	Approved
0.6765	Remote Similarity	NPD3573	Approved
0.6765	Remote Similarity	NPD7524	Approved
0.6759	Remote Similarity	NPD5696	Approved
0.6737	Remote Similarity	NPD3703	Phase 2
0.6735	Remote Similarity	NPD4695	Discontinued
0.6733	Remote Similarity	NPD5329	Approved
0.6726	Remote Similarity	NPD4730	Approved
0.6726	Remote Similarity	NPD4729	Approved
0.6726	Remote Similarity	NPD5128	Approved
0.6701	Remote Similarity	NPD6118	Approved
0.6701	Remote Similarity	NPD6114	Approved
0.6701	Remote Similarity	NPD6115	Approved
0.6701	Remote Similarity	NPD6697	Approved
0.6699	Remote Similarity	NPD6903	Approved
0.6699	Remote Similarity	NPD5737	Approved
0.6699	Remote Similarity	NPD6672	Approved
0.6698	Remote Similarity	NPD5282	Discontinued
0.6667	Remote Similarity	NPD5279	Phase 3
0.6667	Remote Similarity	NPD8377	Approved
0.6667	Remote Similarity	NPD8294	Approved
0.6667	Remote Similarity	NPD6411	Approved
0.6639	Remote Similarity	NPD6335	Approved
0.6636	Remote Similarity	NPD5344	Discontinued
0.6636	Remote Similarity	NPD5695	Phase 3
0.6634	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.6634	Remote Similarity	NPD4197	Approved
0.6612	Remote Similarity	NPD8033	Approved
0.6612	Remote Similarity	NPD8296	Approved
0.6612	Remote Similarity	NPD8379	Approved
0.6612	Remote Similarity	NPD8378	Approved
0.6612	Remote Similarity	NPD8380	Approved
0.6612	Remote Similarity	NPD8335	Approved
0.661	Remote Similarity	NPD6274	Approved
0.6609	Remote Similarity	NPD5251	Approved
0.6609	Remote Similarity	NPD5134	Clinical (unspecified phase)
0.6609	Remote Similarity	NPD5250	Approved
0.6609	Remote Similarity	NPD5249	Phase 3
0.6609	Remote Similarity	NPD5247	Approved
0.6609	Remote Similarity	NPD5248	Approved
0.6609	Remote Similarity	NPD5169	Approved
0.6609	Remote Similarity	NPD6371	Approved
0.6609	Remote Similarity	NPD5135	Approved
0.6598	Remote Similarity	NPD6116	Phase 1
0.6596	Remote Similarity	NPD4809	Clinical (unspecified phase)
0.6596	Remote Similarity	NPD4808	Clinical (unspecified phase)
0.6583	Remote Similarity	NPD7100	Approved
0.6583	Remote Similarity	NPD7101	Approved
0.6571	Remote Similarity	NPD46	Approved
0.6571	Remote Similarity	NPD6698	Approved
0.6562	Remote Similarity	NPD7339	Approved
0.6562	Remote Similarity	NPD6942	Approved
0.6559	Remote Similarity	NPD3699	Clinical (unspecified phase)
0.6559	Remote Similarity	NPD3700	Clinical (unspecified phase)
0.6555	Remote Similarity	NPD6317	Approved
0.6552	Remote Similarity	NPD5216	Approved
0.6552	Remote Similarity	NPD5127	Approved
0.6552	Remote Similarity	NPD5215	Approved
0.6552	Remote Similarity	NPD5217	Approved
0.6535	Remote Similarity	NPD6695	Phase 3
0.6509	Remote Similarity	NPD5284	Approved
0.6509	Remote Similarity	NPD5281	Approved
0.6505	Remote Similarity	NPD4690	Approved
0.6505	Remote Similarity	NPD4519	Discontinued
0.6505	Remote Similarity	NPD4688	Approved
0.6505	Remote Similarity	NPD4623	Approved
0.6505	Remote Similarity	NPD4689	Approved
0.6505	Remote Similarity	NPD5205	Approved
0.6505	Remote Similarity	NPD4138	Approved
0.6505	Remote Similarity	NPD6098	Approved
0.6505	Remote Similarity	NPD4693	Phase 3

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data